Two New Fucose-α (1–2)-Glycans Assigned In The Healthy Human Brain Taking The Number To Seven

Abstract

Fucosylated glycans are involved in the molecular mechanisms that underpin neuronal development, learning and memory. The capacity to study the fucose-α(1–2)-glycan residues noninvasively in the human brain, is integral to understanding their function and deregulation. Five fucose crosspeaks were assigned to fucosylated glycans using in vivo two-dimensional magnetic resonance Correlated SpectroscopY (2D L-COSY) of the brain. Recent improvements encompassed on the 3T Prisma (Siemens, Erlangen) with a 64-channel head and neck coil have allowed two new assignments. These are Fuc VI (F2:4.44, F1:1.37 ppm) and Fuc VII (F2: 4.29, F1:1.36 ppm). The Fuc VI crosspeak, close to the water resonance, is resolved due to decreased T1 noise. Fuc VII crosspeak, located between Fuc I and III, is available for inspection due to increased spectral resolution. Spectra recorded from 33 healthy men and women showed a maximum variation of up to 0.02 ppm in chemical shifts for all crosspeaks.

Towards Mapping of the Human Brain N-Glycome with Standardized Graphitic Carbon Chromatography

“…Guided by reports that brain N-glycans are highly fucosylated and bisected and contain galactose primarily in β1,4-linkage but also, to a smaller extent, in β1,3-linkage [ 9 , 11 ], we bio-synthesized a range of N-glycans containing these structural features in addition to the almost complete set of permutations of glycans with five hexose, four N-acetylhexosamine and one fucose residue (H5N4F1) generated for a recent work [ 28 ]. Some studies also reported α1,2-linked fucose to galactose [ 36 , 37 ] as being present in the brain glycome, so we also biosynthesized structures containing this feature. To consider the possible presence of Lewis A (LeA) determinants, we also synthesized glycans containing this substitution.…”

The N‐glycan profile in cortex and hippocampus is altered in Alzheimer disease

“…For instance, reports from rodent models have shown that it can suppress hippocampal LTP maintenance (Krug et al, 1991), is enriched in certain synaptic proteins (Smalla et al, 1998) (Murrey et al, 2006) and promotes outgrowth of hippocampal neurons (Kalovidouris et al, 2005). Importantly, Fucα(1-2)Gal has also been confirmed to be present in human brain by in vivo two-dimensional magnetic resonance correlated spectroscopy (2D L-COSY), which has been used to assign seven different glycans containing Fucα(1-2) Gal in human brain (Mountford et al, 2015;Tosh et al, 2019).…”

A spoonful of L‐fucose—an efficient therapy for GFUS‐CDG, a new glycosylation disorder

“…An increasing number of fucosylated glycans could be detected in healthy human brains. The fucose residues on the glycans are important for neuronal development, learning and memory (Mountford et al, 2015;Tosh et al, 2019). In a Gfus À/À (formerly Fx À/À ) mouse strain, most of the knockouts were not viable.…”